Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 19-year-old boy, who complained of fever and fatigue was hospitalized in November 1986. On physical examination, he had a temperature of 37 degrees C, cervical lymphadenopathy and hepatosplenomegaly. Serum transaminase was elevated moderately, while serum alkaline-phosphatase was elevated severely. Extremely elevated antibody titers to the EBV capsid antigen (IgG: 2560x, IgA: 160x), early antigen (IgG: 1280x, IgA: 160x) and nuclear antigen (160x) were noted. PPD and DNCB skin test were negative. Severe mobilization of Kupfer cells and mild proliferation of pseudoductule were seen in liver biopsied specimen. Cervical lymphnode biopsy showed necrotizing lymphadenitis associated with proliferation of histiocyte. In February 1987 his temperature was elevated to 40 degrees C and he had arthralgia and exanthema. Intravenous Acyclovir (500 mg every 8 hours) and Interferon alpha (6 million u/day) were administered together for 1 month. After that he improved for about a week. In March 1987 he had dyspnea. Arterial blood gas analysis in room air showed a PO2 of 51.8 mmHg, a PCO2 of 28.9 mmHg. A chest radiograph showed thickening of bilateral bronchial walls and obscurity of pulmonary vascular shadows. The effects of transfer factor and Interleukin-2 were unremarkable. High antibody titers to EBV, liver dysfunction and hypo-oxygenemia continued. He died of respiratory and heart failure on 24 October 1987. The most interesting finding of autopsied specimens was stenosis of pulmonary artery associated with interstitial pneumonitis. Hemophagocytosis was seen in liver, spleen and bone marrow.
 ...
PMID:[An autopsied case of chronic active Epstein-Barr virus (EBV) infection with various symptom]. 164 35

The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted.
 ...
PMID:Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. 220 2

In recent years heart transplantation has become an increasingly common therapeutic measure for cases of heart failure not amenable to other forms of management. Despite major advances, graft rejection continues to be the main cause of transplant failure. To expand our knowledge of the rejection process, we have grown lymphocytes from biopsy specimens obtained from potentially rejecting allografts. The growth of the lymphocytes requires the presence of interleukin-2 and was shown to correlate well with histologic criteria in identifying rejection (p less than 0.003, chi-square analysis). Of 125 biopsy specimens, 61 (49%) became positive for lymphocyte growth within 30 days. Of the biopsy specimens that were positive on culture, 54 (88%) were histologically diagnosed as rejecting, and seven (11%) were histologically nonrejecting. Of the 64 specimens that were negative on culture, 28 (44%) were histologically negative for rejection, and 36 (56%) were positive for some grades of rejection. Of these culture negative, microscopically positive specimens, however, 31 (86%) were associated with mild (grade 3) or equivocal (grade 2) rejection. Discrepancies between culture and histology appeared to be related to degree of rejection, quantity of sample, and sampling variation. Phenotypic identification of cultured cells showed that the suppressor/cytotoxic phenotype was the predominant cell type in all cultures (mean +/- standard error = 83% +/- 3% of cells). Antihuman mature inducer/helper T cell (OKT4+) T-lymphocytes in culture were associated with biopsy specimens obtained immediately before onset or at the beginning of rejection. Preliminary studies testing in vitro sensitivities of lymphocytes to antithymocyte globulin (ATG) and other control immunosuppressants not believed to function by direct cytolysis (methylprednisolone, cyclosporine, azathioprine) were undertaken. These yielded reproducible dose-response curves, and the drug concentration producing 50% cytotoxicity (LD50) was calculated for each drug-culture combination. The mean LD50 for ATG was in the range of in vivo therapeutic concentrations, whereas LD50 values for control drugs were threefold to twelvefold higher than therapeutic concentrations. Resistance to the effects of ATG showed a tendency to correlate with prolongation of rejection; however, a similar tendency was noted for control drugs, suggesting the possibility of a nonspecific mechanism of resistance to the effects of ATG. The technique of interleukin-2 lymphocyte culture from rejecting allografts promises to further our understanding of mechanisms of graft rejection.
 ...
PMID:Propagation and characterization of lymphocytes from rejecting human cardiac allografts. 306 46

Eight patients with advanced cancer of the urinary tract were treated with recombinant interleukin-2(IL-2) at our department between December, 1985 and September, 1987. Patients were given 5 x 10(5)-4 x 10(6) units of IL-2 by intravenous drip infusion daily. One of five patients who received IL-2 for over 28 days showed 62% regression in size of hepatic metastasis of bladder cancer on computed tomography and another showed marked improvement of Performance Status. The upward tendency of natural killer and lymphokine-activated killer activity of peripheral blood was observed during treatment. Fever, mental disturbance, hypotension and eosinophilia and others were recognized during administration of IL-2, and cardiac failure and disturbance of renal function were also recognized as severe side effect.
 ...
PMID:[Treatment of advanced cancer of the urinary tract with interleukin-2 (IL-2)]. 326 12

The objective of this study was to ascertain whether immune abnormalities were present in a group of patients with chronic stable heart failure at a time when sympathetic drive was not excessive. Elevated sympathetic tone not only plays an important role in the pathophysiologic characteristics of congestive heart failure but may also regulate certain aspects of immune function, which has been shown to be abnormal in patients with severe heart failure. Studies have indicated a high incidence of heterophil antibodies against constituents of the heart, the presence of antibody-mediated cytotoxicity against cultured heart cells, and a decrease in suppressor and natural killer-cell function in patients with idiopathic dilated cardiomyopathy. Lymphocytes were separated over a Ficoll-Hypaque gradient. Lymphocyte subtypes and well as interleukin-2 receptors were detected by means of mouse monoclonal antibodies conjugated with fluorescein or phycoerytherin, and immunofluorescence was measured with a flow cytometer. Mitogen proliferation was assessed by tritiated thymidine incorporation in the presence of either conconavalin A or tetanus toxoid. Serum was used in conjunction with iodine 125-labeled iodopindolol binding to rat cardiac membranes to attempt to detect beta-receptor antibodies. In patients with ischemic (n = 21) and idiopathic (n = 16) cardiomyopathy, the norepinephrine levels were modestly elevated (idiopathic = 482 +/- 70 pg/ml; ischemic = 501 +/- 45 pg/ml) compared with control subjects without heart disease (n = 10; norepinephrine = 252 +/- 70 pg/ml). We found no differences in the number and subtypes of circulating lymphocytes in the three groups, and there was no serum inhibition of beta-binding to rat cardiac membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Immune function in patients with chronic stable congestive heart failure. 838 25

Interleukin-2 (IL-2) is a cytokine with proven activity against metastatic renal cell carcinoma (RCC) and malignant melanoma (MM). The intravenous administration of high-dose IL-2 is limited by important cardiovascular side effects such as hypotension, fluid retention, arrhythmias, and myocardial ischemia, which often cause dose reduction and/or treatment withdrawal. The occurrence of these toxic events is not predicted by routine pretreatment examinations. The aim of the present study was to test the reliability of serial echocardiography in predicting subsequent cardiac adverse effects in patients undergoing IL-2 administration. In 19 patients (15 men, 4 women; median age: 51 years, range 27-71 years; 10 affected by metastatic RCC and 9 affected by MM) we performed two-dimensional and Doppler echocardiography before and immediately after 28 continuous intravenous infusions (CIVI) of IL-2 at the dose of 18 MIU/m2/day for 4 days. Left ventricular systolic function and the diastolic transmitral flow pattern were assessed before and after IL-2 administration. Significant changes of two indexes of left ventricular filling were noted: a decrease of the ratio of maximal flow velocity in early diastole to that in late diastole (E/A) (basal: 1.12 +/- 0.46, mean +/- SD; posttreatment: 0.83 +/- 0.27; p < 0.01) and an increase of the percentage of the atrial contribution to left ventricular filling (basal: 37.75 +/- 11.58%; posttreatment: 49.43 +/- 16.48%; p < 0.01). Eight major cardiovascular events causing IL-2 infusion withdrawal were observed (two ischemic electrocardiographic modifications, three grade III-IV hypotension, one atrial fibrillation, one pericardial effusion, one acute heart failure). These major cardiovascular events were observed more often when an abnormal basal E/A ratio < 1.0 (p < 0.05) was found. We conclude that Doppler transmitral flow pattern analysis before and subsequent to IL-2 infusion is a useful and easily available procedure for the monitoring of cardiac modifications during CIVI IL-2 administration. It might also predict a major cardiovascular event during IL-2 administration. Patients with basal E/A ratio < 1.0 should be more carefully monitored during treatment and/or should be treated with lower IL-2 doses to avoid cardiovascular toxicity.
 ...
PMID:Isolated left ventricular filling abnormalities may predict interleukin-2-induced cardiovascular toxicity. 873 96

Heart failure is a complex neurohumoral and inflammatory syndrome. Studies have shown that proinflammatory cytokines (interleukin-1, interleukin-2, interleukin-6, and tumor necrosis factor) are involved in cardiac depression and in the complex syndrome of heart failure. Understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure with the use of monoclonal antibodies directed against specific cytokines that may block the downhill progression of heart failure.
 ...
PMID:Role of cytokines in heart failure. 948 63

BACKGROUND-Myocardial failure is an important problem after heart transplantation. Right ventricular (RV) failure is most common, although its mechanisms remain poorly understood. Inflammatory cytokines play an important role in heart failure. We studied the expression of tumor necrosis factor (TNF)-alpha and other cytokines in donor myocardium and their relationship to the subsequent development of RV failure early after transplantation. METHODS AND RESULTS-Clinical details were obtained, and ventricular function was assessed by transesophageal echocardiography in 26 donors before heart retrieval. A donor RV biopsy was obtained immediately before transplantation, and each recipient was followed for the development of RV failure. Reverse transcriptase-polymerase chain reaction was performed to detect TNF-alpha, interleukin-2, interferon-gamma, and inducible nitric oxide synthase expression. Eight of 26 recipients (30.8%) developed RV failure. Seven of these 8 (87.5%) expressed TNF-alpha, but only 4 of the 18 (22.2%) who did not develop RV failure expressed TNF-alpha (P<0.005). As a predictor of RV failure, TNF-alpha mRNA had a sensitivity of 87.5%, a specificity of 83.3%, a positive predictive value of 70%, and a negative predictive value of 93.7%. Western blotting demonstrated more TNF-alpha protein in the myocardium of donor hearts that developed RV failure (658+/-60 versus 470+/-57 optical density units, P<0.05). Immunocytochemistry localized TNF-alpha expression to cardiac myocytes. Reverse transcriptase-polymerase chain reaction detected interferon-gamma in 2 (7.7%), interleukin-2 in 1 (3.8%), and inducible nitric oxide synthase mRNA in 1 (3.8%) of the 26 donor hearts, none of which developed RV failure. CONCLUSIONS-TNF-alpha expression in donor heart cardiac myocytes seems to predict the development of RV failure in patients early after heart transplantation.
 ...
PMID:Tumor necrosis factor-alpha is expressed in donor heart and predicts right ventricular failure after human heart transplantation. 1089 97

Heart failure is a complex neurohumoral and inflammatory syndrome. Recent studies have shown that proinflammatory cytokines (interleukin-1, interleukin-2, interleukin-6, interleukin-10, and tumor necrosis factor) are involved in cardiac depression and in the complex syndrome of heart failure. Understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure by the use of monoclonal antibodies directed against specific cytokines to block the downhill progression of heart failure.
 ...
PMID:Pathophysiological role of cytokines in congestive heart failure. 1116 Jul 65

Dilated cardiomyopathy is a cardiac disease of unknown origin which is characterized by the gradual development of cardiac failure associated with four-chamber dilatation of the heart. Heart transplantation has been considered as the last resort for this disease. However, some patients who received support with a ventricular assist device (VAD) as a bridge-to-transplantation and then recovered without transplantation have been reported. This new concept of treating heart failure is termed bridge-to-recovery. A VAD can inhibit the heart failure compensatory mechanisms by extreme ventricular unloading. Also, heart failure is a complex neurohormonal/autocrine-paracrine syndrome, and these mechanisms consecutively lead to inflammatory response by proinflammatory cytokines; interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Furthermore, the existence of anti-beta1-adrenoceptor autoantibodies (A-beta1-AABs) in a patient with dilated cardiomyopathy has been reported. These proinflammatory cytokines and this antibody accelerate a ventricular remodeling and a contractile dysfunction over the long term. Apheresis can also inhibit the vicious cycle in heart failure by removing the factors that are produced by activated neurohormonal/autocrine-paracrine compensatory mechanisms. Therefore, we propose that the combined therapies, therapeutic VAD and therapeutic apheresis, will provide a prominent outcome for a patient who is suffering from end-stage heart failure.
 ...
PMID:Combination of therapeutic apheresis and therapeutic ventricular assistance for end-stage heart failure patients. 1216 92


1 2 3 Next >>